Hepatitis C: A Closer Look

Many people living with HIV must deal with not only one virus, but also with a co-traveler: hepatitis C virus (HCV), which infects liver cells. For some, the liver is only slightly damaged since it is able to make new cells and bounce back. But for others, HCV infection can lead to cirrhosis (severe liver damage), and the liver can lose some or all of its function. Finally, HCV may cause cancer of the liver and liver failure in some people.

A Global Epidemic

Worldwide, 130 million people have HCV, though the vast majority don't know it. In fact, 27% of people with cirrhosis and 25% of those with liver cancer have these serious problems due to HCV. The good news is that since 1989 we've seen the number of new cases of hepatitis C in the U.S. simmer down to about 20,000 new cases each year, drastically lower that the 230,000 new cases we saw each year during the 1980s. HCV still accounts for up to 13,000 deaths each year in the U.S., however, and is responsible for the majority of liver transplants. Each year, complications and deaths associated with HCV infection are higher than in the previous year, and are now a growing concern in the HIV community.

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In the U.S, about 30% of people with HIV also have HCV, and in some populations up to 90% of people who got HIV from sharing needles also have HCV. This is due largely to the fact that HCV most easily enters the body through the bloodstream. HIV can also enter the body in this way, which is why infection with both viruses is not uncommon. Yet there do seem to be some differences between the two.

Compare and Contrast

Both HIV and HCV carry their genes in the form of RNA (the mirror image of the DNA found in most viruses). However, the similarities seem to end there. HCV is a smaller virus, but can churn out many more copies a day (up to a trillion) than can HIV. It is also much more resilient than HIV. For example, HCV can still be infectious even in a dried droplet of blood, whereas HIV is often noninfectious seconds after it reaches the air. And while both can be transmitted through blood (sharing needles, for example), HCV is about ten times more infectious than HIV. Simply put, if 100 people are actively sharing needles for one year, 64 will test positive for HCV, but only 14 will test positive for HIV. For a smaller virus, HCV certainly gets a run for its money.

Blood to Blood

By far the most efficient way for HCV to enter the body is through direct blood-to-blood contact. This is usually due to sharing injection equipment, but in some areas of the world can still happen through transfusions or organ transplants. Before 1992, people with hemophilia and individuals receiving transfusions were at great risk for hepatitis C infection -- 84-100% of hemophiliacs and 10% of people receiving blood transfusions received blood products infected with HCV. Today, in the U.S. and many other countries, the risk of contracting HCV through transfusions and blood products has been virtually eliminated. The risk of HCV transmission has become less than one in a million per unit of blood transfused, thanks to the screening of blood donations for HCV that began in the summer of 1992.

Organ transplants have also been cited as carrying a high risk of HCV transmission. Studies have found that three out of every four people who received an organ (kidney, heart, or liver) from a donor who had HCV also developed HCV antibodies, and about a third developed liver disease. As a result, transplant centers have developed protocols to include screening for hepatitis C that prevent infected organs from being used.

While concern about accidental needlesticks is justified, the actual risk of getting hepatitis C this way is extremely low. Studies that have looked at the number of reported cases have found that only 1% of accidental needlesticks lead to HCV infection. Solid needles (used for tattoos and acupuncture) seem to carry a lower risk of transmission than hollow needles (used for blood samples and infusions). While both types have a low risk of infection, care should be taken to avoid needlesticks and to ensure that sterile needles and ink are used for tattooing and piercing.

Heterosexual Transmission

There's a lot of discussion surrounding the degree to which HCV can be transmitted through sex. We know that hepatitis C can be spread sexually, but how often does it happen? In short, not that often when it comes to vaginal intercourse. One study looked at 500 heterosexual couples in which one partner was HCV positive, and who had been monogamous and sexually active without condoms. The results were quite optimistic: only five cases of transmission appeared to have occurred after 16 years. A second study of 895 monogamous, heterosexual couples who did not use condoms or have anal sex or sex during menstruation found three of the negative partners became HCV positive, but none had the same type of virus as their partner, meaning they most likely got it some other way. Overall, only 1 in 1000 couples, or 0.1%, reported having gotten the virus through sexual transmission. Therefore, while vaginal sexual transmission is possible, the risk of infection appears to be quite low, particularly among monogamous couples.

What happens when someone is living with HIV as well? How does this change the risk of transmission? In certain people with HIV, such as heterosexual couples and expectant mothers, we see higher levels of HCV transmission. In one study, about twice as many heterosexual partners became positive for hepatitis C when their partners had both HCV and HIV. This study also found that among those who became HCV-positive, having multiple sex partners, a history of sexually transmitted diseases, or not using condoms increased their risk for hepatitis C. Therefore, while sexual transmission carries an extremely low risk overall, it is higher among heterosexual couples where one person is living with both viruses.

Pregnancy

Heterosexual couples aren't the only group whose HCV risk seems to increase with HIV infection. Pregnant women are also affected. In women with HCV only, 5% will transmit HCV to their newborns, but for women with both viruses, that number quadruples to 19%. In fact, a review of all studies on mother-to-child HCV transmission found that having HIV was the greatest factor associated with hepatitis C transmission. Other factors include a higher level of HCV at the time of delivery, especially when the hepatitis C viral load is greater than 100,000. Studies have also been done to examine whether Cesarean delivery would lower transmission, but so far this has not been shown to have an added benefit. Breastfeeding also does not appear to be a significant means of HCV transmission, but is not recommended for women living with both viruses because of the risk of HIV transmission.

Male-to-Male Transmission

Up to 4% of men who have sex with men (MSM) have hepatitis C. A few factors have been associated with higher rates of hepatitis C transmission, including unprotected anal sex, fisting, group sex, use of recreational drugs that lower inhibitions, and having a sexually transmitted disease (such as syphilis). It's not certain that HIV increases the risk of HCV transmission in MSM, but recent reports from Europe of HIV-positive men becoming infected with HCV suggest that having HIV may be a factor. A small study in Australia looked at 26 HIV-positive and 94 HIV-negative MSM and found only one case of HCV infection among the HIV-negative men (1%), but 13 among the HIV-positive men (50%).

Several factors may be associated with having both viruses, including unprotected rough sex and having a greater number of sexual partners, along with any of the risk factors listed above. More specifically, one study that looked at 1,836 MSMs in Amsterdam found that as of the year 2000, 56% of men with both HIV and HCV who did not use injection drugs reported having unprotected rough sex. Genital ulcers may additionally increase one's risk; one study found that 90% of men who became recently infected with HCV had ulcers.

While these risk factors are cause for concern, other studies have found that the overall number of MSM with hepatitis C is not higher than that of heterosexual men. A study of 3,455 heterosexual men and 1,699 MSM in U.S. public health clinics from 1999 to 2003 (who didn't report injection drug use) found that the straight men were actually twice as likely to have HCV (3.6% compared to 1.5%).

But this may be changing. A study in England looked at 7,169 MSM who reported no injection drug use. HCV incidence increased from zero in 2002 to 3.6 per 1,000 patient-years in 2006. HIV-positive men were found to be about 13 times more likely to have a new HCV diagnosis compared with HIV-negative men.

Living With HCV

Once HCV has entered the bloodstream, the virus seeks out liver cells (hepatocytes), where it can set up shop. Unlike HIV, HCV does not need to enter a cell's nucleus, where the cell's DNA is stored. Instead, it stays in the main body of the cell -- the cytoplasm. Over time, hepatocytes can become overwhelmed by the toll of the infection and can become damaged, or fibrotic. Liver tissue can scar, and over time can lead to cirrhosis, in which liver cells lose function and can die.

During this time, the liver will try to replace the damaged and dead cells, and in the process spill out enzymes called ALTs and ASTs, both of which can be measured in blood tests called liver function tests. Higher levels of ALTs and ASTs are sometimes the only sign of infection with hepatitis C, as many people can live 10 to 20 years without any other signs or symptoms. Other signs can include yellowing of the whites of the eyes or skin (jaundice), fluid in the belly (ascites), and dark urine or pale stools.

Of 100 people infected with HCV only, roughly 20 will completely clear the virus on their own. But that means that 80 of the 100 will have it for many years. Of those, about 30 will stay stable and healthy; 50 will develop fibrosis, 16 of whom will also develop cirrhosis; four will develop liver cancer; and one will die from liver disease. While only a small number of people with HCV will progress to cirrhosis, it is important to for each person to be aware of the risk factors for disease, as most people living with hepatitis C will not have any symptoms but may still be progressing in their disease. Also, other cofactors, such as HIV or alcohol use, increase the risk that someone will progress to more serious liver disease.

Progression of HCV Monoinfection Over 10-25 Years

These numbers are rough estimates based on people with HCV only. Cofactors like HIV infection or alcohol use increase the risk of disease progression.

Watching the Viruses

How should liver health be monitored in someone who has hepatitis C? Well, since HCV nestles into liver cells, monitoring ALT and AST levels in the blood can give a clue as to whether there is any liver damage at the moment. But while infection with HCV can raise these enzymes over time, other things can, too. For example, certain medications (including Tylenol and many HIV meds) are broken down in the liver and can affect overall liver health. Monitoring liver enzymes every 3 to 6 months can help keep tabs on how the liver is handling the virus and any other pressures it has on it at the time.

But monitoring liver enzymes is not enough, since these tests may be in the normal range even though hep C is doing damage. A few other tests are needed, especially if someone is also considering starting treatment. Viral load tests are available that can tell us how much HCV virus is in a milliliter of blood. While viral loads are routinely measured in HIV disease, for hepatitis C these tests are most helpful before starting HCV treatment and for seeing how well it is working. Someone who has less than 2 million copies (or 800,000 international units) of HCV is considered to have low levels of virus. More than 2 million copies is considered a high viral load. Again, this is useful for making decisions about treatment, but repeated HCV viral loads are not routinely done, since levels of HCV often remain stable, keeping viral loads quite consistent from year to year.

If someone is considering treatment, two additional tests are useful: a genotype test and a liver biopsy. An HCV genotype test is different from an HIV genotype test (which looks for drug resistance). An HCV genotype test identifies which strain of HCV a person has. There are six types (or strains) of HCV, numbered 1 to 6. About 75% of people with HCV in the U.S. have type 1. In Europe, on the other hand, type 2 is more common. Knowing the genotype is useful, since studies have found that people with type 2 or 3 tend to do better on treatment than type 1. So knowing your genotype can help you and your doctor get a feel for how useful treatment might be. (See "Hepatitis C Treatment Today.")

Liver biopsies are by and large the gold standard for making decisions about when to start treatment, as they give us the clearest feel for how much liver damage there is. An ultrasound of the liver is often done before a biopsy to find the best place in the liver to collect a sample. Then, using a needle that is inserted just below the right ribs, a small piece of the liver is snipped out and looked at under the microscope. This can tell whether a liver has mild, moderate, or severe damage, which is very useful as a patient and doctor decide whether treatment is needed. While any biopsy is invasive, this procedure is usually done on an outpatient basis, is not painful in most cases, and has complications only rarely. The main risk is internal bleeding, so physicians will often ask you to stay at the office for several hours to monitor for any bleeding.

In a nutshell, it is useful to monitor liver enzymes (ALT, AST) routinely every 3 to 6 months. When considering treatment, it may also be useful to have viral loads, genotype testing, and a liver biopsy, as all three provide valuable information about liver health. None of these tests can predict what's going to happen with the liver, but they give valuable information about how the liver is responding to the virus.

Conclusions

Hepatitis C remains an important health issue for many populations, including people with HIV. Given the potential for long term liver disease, a thorough understanding of how hepatitis C is transmitted, and how it is affected by HIV, can be helpful in the long term management and care of people living with both viruses.

Donna M. Kaminski, ACRIA's former Associate Director of Treatment Education, is currently a third-year medical student.

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